- A phase 3 clinical study published in the New England Journal of Medicine showed an average 14.9% decrease in body weight in obese or overweight adults who received an injectable diabetes drug, semaglutide, in addition to their lifestyle interventions.
- About 50% of the participants in the semaglutide group achieved significant weight reductions of 15% or more, while 69% of the participants achieved 10% or more and 86% of the participants achieved 5% or more.
- The study showed a reduction in risk factors for diabetes and heart disease, as well as better physical functioning in participants who received semaglutide.
Obesity is a widespread and serious health problem in both the US and around the world. The Centers for Disease Control and Prevention (CDC) reports that the prevalence of obesity in the US increased significantly from 30.5% in 1999 to 2000 to 42.4% in 2017 to 2018, with the The number of severe obesity has increased from 4.7% to 9.2%.
Doctors often use Body Mass Index (BMI), which a person can calculate by dividing their weight in kilograms (kg) by the square of their height in meters, to determine whether a person’s weight is healthy. A BMI from 25 to
Obesity decreases life expectancy and is a major risk factor for cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and certain cancers, including breast, ovarian, endometrial, prostate, liver, and colon cancers.
Currently, a combination of diet and exercise is the mainstay of obesity treatment. If these lifestyle interventions prove ineffective over a 6 month period, clinical guidelines recommend medication for people with a BMI ≥ 30 or for people with a BMI ≥ 27 who have other related health conditions.
Efficacy, cost, and safety issues limit the use of currently available drugs. Injectable semaglutide is a drug that the Food and Drug Administration (FDA) has approved for adults with type 2 diabetes and cardiovascular disease.
Semaglutide is an analog of the naturally occurring human glucagon-like peptide-1 (GLP-1) hormone in the body. After meals, the body releases GLP-1 from the intestines into the bloodstream, which increases the feeling of satiety and reduces hunger and cravings.
In a phase 2 clinical trial in adults with type 2 diabetes and obesity, injectable semaglutide treatment resulted in weight loss.
This finding prompted researchers to conduct a global phase 3 study, called Semaglutide Treatment Effect in People with Obesity (STEP), to evaluate the safety and effectiveness of semaglutide in participants 18 years and older.
Participants either had a BMI ≥ 30 or a BMI ≥ 27 and weight-related health conditions. One group of participants received placebo instead of treatment.
The study excluded people who had diabetes, had previously had bariatric surgery, or had used drugs to treat obesity in the 90 days prior to registration. However, participants had some weight-related health conditions, including high blood pressure, high cholesterol, obstructive sleep apnea, and cardiovascular disease.
The researchers randomly assigned a total of 1,961 participants to receive either semaglutide (injected under the skin at a dose of 2.4 milligrams) or placebo, with both groups also receiving lifestyle interventions.
For 68 weeks, 1,306 participants received semaglutide and 655 participants received placebo weekly.
At the start of the study, the average body weight was 105.3 kg, the average age 46 years and the average BMI 37.9. In addition, 75% of participants had at least one concurrent illness.
On average, participants in the semaglutide group significantly reduced their body weight by 14.9% (-15.3 kg) from baseline, compared with 2.4% (-2.6 kg) in the placebo group.
The study showed significant weight reductions from:
- 5% or more in 86.4% of participants in the semaglutide group versus 31.5% in the placebo group
- 10% or more in 69.1% of participants in the semaglutide group versus 12% in the placebo group
- 15% or more in 50.5% of participants in the semaglutide group versus 4.9% in the placebo group
Study participants who received semaglutide also showed greater reductions in waist circumference, blood pressure, fasting lipid levels, and blood sugar than those who received the placebo. In addition, they had increased their self-reported physical function values.
The most common side effects were mild to moderate nausea and diarrhea, which usually went away over time. In the semaglutide group (4.5%), more participants discontinued treatment due to gastrointestinal side effects than in the placebo group (0.8%).
The study had a number of limitations, including its short duration and the exclusion of people with diabetes.
The majority of participants were white (75.1%) and female (74.1%) and therefore did not reflect the general obese population. This limits the generalizability of the results.
In addition, people with a needle phobia may not want to use an injectable drug in the long term.
One of the study’s lead authors, Rachel Batterham, MB, BS, Ph.D., Professor of Obesity, Diabetes and Endocrinology at the Center for Obesity Research at University College London (UCL) and the UCL Hospitals Center for Weight Management, comments on the results:
“No other drug has come close to achieving this weight loss – this really is a game changer. For the first time, people can achieve through medication what only weight loss surgery could do. “
Based on these study results, Novo Nordisk, the pharmaceutical company funding the clinical trial, filed with the FDA, the European Medicines Agency, and the National Institute for Health and Care Excellence for regulatory approval of injectable semaglutide for the treatment of obesity.
Although the study results appear promising, head-to-head studies will be needed to compare semaglutide with other pharmacological and surgical treatment options to determine its possible role in treatment.
Dr. Batterham adds, “The health effects of obesity have been brought to the fore by COVID-19, where obesity significantly increases the risk of dying from the virus and increases the risk of many life-limiting serious illnesses, including heart disease, Type 2 diabetes, liver disease, and certain types of cancer. ”
“This drug could have a significant impact on UK health policy in the years to come.”